Does Blood NAD+ Actually Fall With Age? Seven Human Cohorts Say No
A 2026 Nature Metabolism study measured NAD+ across seven human cohorts and found whole-blood levels stable with age. What that does and does not mean.
Much of the NAD+ category rests on one sentence: NAD+ declines with age, therefore raising it again should help. It is repeated across this market, ours included until recently, and repeated often enough that the number behind it rarely gets questioned.
In May 2026, a group at Amsterdam UMC went and measured it properly. Across seven independent human cohorts, using a method built specifically to survive the ways NAD+ measurement usually goes wrong, they found that whole-blood NAD+ does not fall with age at all.
This article is about what that study actually shows, and just as importantly, what it does not.
TL;DR: The 2026 blood-NAD+ finding
The study: Nature Metabolism, June 2026 issue (epub 14 May), Trętowicz et al., Houtkooper lab, Amsterdam UMC (PMID 42135539). Seven independent human cohorts, quantified with a rigorously validated UHPLC-HRMS method. The result: whole-blood NAD+ levels "remain remarkably stable with age and across lifestyle interventions", while still changing in response to nicotinamide riboside supplementation, as expected. The authors' conclusion, verbatim: the results "challenge the utility of blood NAD+ levels as a biomarker of ageing or lifestyle factors". The scope, which matters enormously: the study measured blood, not tissue. It does not refute the tissue-level decline that motivates the restoration hypothesis. The companion finding: in a 2026 phase 2 trial (PMID 42009009), nicotinamide riboside plus exercise beat control, but was not statistically different from exercise alone (p=0.49).
Why This Was an Open Question at All
Here is the part that gets skipped: measuring NAD+ in a human being is genuinely difficult, and the difficulty is not a technicality.
NAD+ is a notoriously fragile analyte, and the standard account of why is that it degrades under ordinary sample-handling conditions at rates that depend on how the sample was collected, processed and stored. On that account two labs measuring the same person can get different answers, not because either is incompetent, but because the analyte is disappearing while they work. That mechanism is background from the wider literature rather than something this paper set out to establish; what the paper itself says is narrower.
The consequence is that the literature on blood NAD+ and age has been a mess. The study's own opening sentence says so plainly: NAD+ levels in blood and tissues "are widely proposed to decline with age, yet evidence in human blood is inconsistent".
That word, inconsistent, is the whole reason the study exists. The premise was not established. It was assumed.
What the method actually was
The authors used ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLC-HRMS), and describe it as "rigorously validated" and built to account for "real-world analytical variability".
That phrase is the study's engineering, not its marketing. It means the method was designed to work under the conditions real samples are collected in, rather than under ideal ones. If the historical inconsistency was an artefact of measurement, a method built to absorb that variability is well suited to reassessing it.
They then applied it across seven independent human cohorts, which is what makes the result hard to wave away as a quirk of one population.
What They Found
Three findings, and the third is the one that makes the first two credible.
Whole-blood NAD+ did not track age. Across the cohorts, levels stayed, in the authors' words, "remarkably stable with age".
It did not track lifestyle interventions either. Same stability across those.
But it did change in response to nicotinamide riboside supplementation, "as expected".
That third point is what makes the first two harder to dismiss, though this reading is ours and not something the paper spells out. The paper reports two things side by side: no change across age or lifestyle, and a change after nicotinamide riboside supplementation. Draw whatever inference you like from that pairing; the paper itself does not present it as a sensitivity argument.
The authors' conclusion follows directly: the results "challenge the utility of blood NAD+ levels as a biomarker of ageing or lifestyle factors".
What This Does Not Mean
This is the section that separates an honest reading from a useful headline, and it needs to be read as carefully as the finding itself.
The study measured blood. It did not measure tissue.
The restoration hypothesis is not primarily a claim about blood. It is a claim about tissues: that NAD+ falls in muscle, liver, brain and elsewhere with age, and that consequences follow from that. This study did not test tissue NAD+ and therefore cannot refute it.
So the correct reading is narrow and specific, and it is worth using the authors' own words: their results "challenge the utility of blood NAD+ levels as a biomarker of ageing or lifestyle factors". The tissue-level premise is untouched by this paper. Anyone citing it as "NAD+ does not decline with age, the whole field is over" is overclaiming in the opposite direction, and that is just as wrong as the marketing it is reacting to.
What it does, in the authors' own words, is "challenge the utility of blood NAD+ levels as a biomarker of ageing or lifestyle factors", and with that, any commercial claim resting on such a measurement.
It also does not show that precursors do nothing. The study found that blood NAD+ does change in response to nicotinamide riboside supplementation, as expected. Whether that change produces an outcome anyone cares about is a different question, and one this paper does not address.
We cover the broader NAD+ picture, including the injectable-versus-oral distinction that most of this market blurs, in our NAD+ 2026 overview, and the precursor comparison in NAD+ vs NMN vs NR.
The Companion Trial, and Its Stage 2 Result
In its May 2026 issue, The Lancet Neurology published a trial that deserves to be read alongside it (PMID 42009009). It is the strongest recent controlled test of an NAD+ precursor we are aware of, albeit in a rare-disease population, and its headline result is not the one that circulated.
The design was unusually clean: a 12-week, phase 2, single-centre, 2 x 2 factorial randomised controlled trial at the Children's Hospital of Philadelphia (NCT04192136), in people aged 10 to 40 with Friedreich's ataxia, a rare inherited neurodegenerative condition in which cardiopulmonary fitness is characteristically low. Seventy-four were enrolled, 66 were randomised to one of four arms: placebo only, oral nicotinamide riboside only, exercise only, or both. The primary outcome was change in peak VO2 (litres per minute) at 12 weeks.
A 2 x 2 factorial is the right design here precisely because it can answer the question a single-arm study cannot: is the precursor adding anything, or is the exercise doing the work?
The stage 1 results, versus control:
- Difference vs control
- 0.10 (95% CI -0.05 to 0.26)
- p (adjusted)
- 0.188, not significant
- Difference vs control
- 0.16 (95% CI 0.00 to 0.31)
- p (adjusted)
- 0.103, not significant
- Difference vs control
- 0.21 (95% CI 0.05 to 0.36)
- p (adjusted)
- 0.0299, significant
Read on its own, that last row is a positive trial, and that is how it largely travelled.
Then comes stage 2, which the trial pre-specified precisely to stop that misreading. It compared the combination against exercise alone. From the paper: "Combination therapy was not statistically different from exercise alone (difference -0.05 ([95% CI -0.10 to 0.21]; p=0.49)." (the stray parenthesis is the source's own)
The precursor did not beat exercise on its own. The honest one-line summary of that trial is that it could not show the precursor adding anything over the exercise.
Read this trial at the right altitude
Friedreich's ataxia is a rare neurodegenerative disease and this was a 12-week phase 2 trial in 66 people. The findings cannot be assumed to generalise to healthy ageing, and nothing here is a treatment claim. The authors' own interpretation is that the combination was safe and increased cardiopulmonary fitness in this population, and that longer studies are needed.
The trial used oral nicotinamide riboside, not injectable NAD+. Dosing was weight-based (300 mg for 24 to 48 kg, 600 mg for 48 to 72 kg, 900 mg above 72 kg), and that is stated here only as a record of what the trial administered, not as guidance of any kind.
On tolerability: all adverse events were mild or moderate, including gastrointestinal symptoms, falls, upper respiratory infections and skin rashes. Rates were not higher in the treated arms than in control (at least one moderate adverse event of interest in 7 of 17 control participants and 6 of 17 on nicotinamide riboside alone), but note what those counts rest on: a difference of one person, in arms of seventeen. The trial did not test adverse-event rates for statistical difference, and these numbers are far too small to support any tolerability conclusion.
Why We Are Publishing This
A fair question: we sell NAD+. Why would we publish two findings that make the category's central sales pitch look thinner?
Because the alternative is worse. The premise "NAD+ falls with age, so raise it" was in our own article too, stated without qualification, in an article published eight days after the Nature Metabolism paper came out. We have corrected it. The correction is not a favour to anyone; it is the minimum standard for a page that claims to report research.
There is also a structural point worth being blunt about. A shop whose whole story is "NAD+ declines, buy NAD+" has little incentive to publish this study, because the study is inconvenient for the story. We would rather publish it, and that is a difference worth having between a research supplier and a supplement seller. If our pages are only trustworthy when the evidence flatters us, they are not trustworthy.
What we think the honest position is
The authors conclude that their results challenge the utility of blood NAD+ as an ageing biomarker, across seven cohorts with a validated method. That is their framing, and it is narrower than "blood NAD+ is useless".
Tissue NAD+ decline remains a live hypothesis, and it is the one the field actually rests on. It was not tested here.
The strongest recent controlled trial of a precursor we are aware of could not separate it from exercise. That is a real result, not a smear, and it should temper expectations rather than end the conversation.
To our knowledge, as of July 2026, none of the compounds discussed here is authorised as a medicine in the EU for ageing or cognition. They are sold here as research materials, and nothing on this page is a therapeutic claim.
Products and Categories Referenced
Research-use-only materials relevant to this article. Their inclusion is not a claim that any of them does anything to human ageing.
Mitochondrial function, NAD+ metabolism, telomere maintenance
Essential cellular coenzyme that declines with age. Powers energy metabolism in every cell, activates sirtuins (longevity genes), and supports DNA repair. A cornerstone molecule in aging and longevity research.
Mitochondrial-derived signaling peptide (16 amino acids) that mimics the effects of exercise at the cellular level. Activates AMPK, improves glucose uptake, and enhances fat metabolism - a key tool in metabolic and longevity research.
Mitochondria-targeted tetrapeptide (Elamipretide) that stabilizes cardiolipin and prevents ROS formation at the source.
Tetrapeptide (Ala-Glu-Asp-Gly) that activates telomerase, the enzyme responsible for maintaining telomere length. One of the most studied peptides in longevity research, developed by Prof. Khavinson at the St. Petersburg Institute of Bioregulation.
The compound discussed here
Other mitochondrial research peptides
Mitochondrial-derived signaling peptide (16 amino acids) that mimics the effects of exercise at the cellular level. Activates AMPK, improves glucose uptake, and enhances fat metabolism - a key tool in metabolic and longevity research.
Mitochondria-targeted tetrapeptide (Elamipretide) that stabilizes cardiolipin and prevents ROS formation at the source.
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